Radiosensitivity index predicts for survival with adjuvant radiation in resectable pancreatic cancer

Radiother Oncol. 2015 Oct;117(1):159-64. doi: 10.1016/j.radonc.2015.07.018. Epub 2015 Jul 30.

Abstract

Background and purpose: Adjuvant radiation therapy for resectable pancreatic cancer remains controversial. Sub-populations of radiosensitive tumors might exist given the genetic heterogeneity of pancreatic cancers. We evaluated whether RSI is predictive of survival in pancreatic cancer treated with radiation.

Materials and methods: We identified 73 genomically-profiled pancreas cancer patients treated with upfront surgery between 2000 and 2011 (48 radiation, 25 no radiation). Briefly, RSI score is derived from the expression of 10 specific genes and a linear regression algorithm modeled on SF2 of 48 cancer cells. The primary endpoint was to assess the association of RSI with overall survival.

Results: Median follow-up was 67months for surviving patients. On multivariate analysis, patients with radioresistant tumors had a trend toward worse survival (Hazard ratio [HR] 2.1 [95% CI 1.0-4.3], p=0.054). Among high-risk, irradiated patients (positive margins, positive lymph nodes, or a post-operative CA19-9 >90; n=31), radiosensitive patients had significantly improved survival compared with radioresistant patients (median 31.2 vs. 13.2months; HR 0.42 [0.19, 0.94], p=0.04). Among irradiated patients (n=48), low-risk patients lived longer than both high-risk patients with radiosensitive tumors and radioresistant tumors (HR 2.7 [1.0, 7.2], p=0.04 and HR 6.3 [2.3, 17.0], p<0.001, respectively).

Conclusions: Integrating RSI with standard high-risk variables has the potential to refine the classification of high-risk resected pancreatic cancer patients treated with radiation therapy.

Trial registration: ClinicalTrials.gov NCT01754623.

Keywords: Cancer; Pancreas; Radiation; Radiosensitivity; Surgery; Survival.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Female
  • Follow-Up Studies
  • Gene Expression
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / radiotherapy*
  • Pancreatic Neoplasms / surgery
  • Pancreaticoduodenectomy / methods
  • Prognosis
  • Proportional Hazards Models
  • Radiation Tolerance / genetics*
  • Radiotherapy, Adjuvant

Associated data

  • ClinicalTrials.gov/NCT01754623